The long-term goal of this research project will be an investigation of the mechanisms and control of protein synthesis in mitochondria isolated from skeletal muscle. In a recent study, we observed that the rates of protein synthesis measured under optimal conditions in vitro were decreased over 60% in skeletal muscle mitochondria isolated from diabetic rats as compared to mitochondria from control rats. This observed decreased rate of mitochondrial protein synthesis in the skeletal muscle of the diabetic may result from a number of changes such as lowered levels of intramitochondrial ATP necessary to maintain protein synthesis. Alternately, the lowered rates of protein synthesis by cytoplasmic ribosomes of skeletal muscle in the diabetic may act to depress the rate of mitochondrial protein synthesis. Experimental evidence obtained with yeast cells undergoing glucose derepression has led to the suggestion that the synthesis of mitochondrial protein may be controlled by proteins synthesized in the cytoplasm. Skeletal muscle mitochondria may be an ideal system in which to explore the precise mechanism of these controls. In any event, the alterations in mitochondrial structure and function which would cause as a result of lowered skeletal muscle mitochondrial protein synthesis may contribute to the considerable muscle wasting which occurs in the diabetic state.